PROJECT SUMMARY/ABSTRACT PEEL Therapeutics, Inc. is a life sciences company created to impact the lives of people with cancer. Based on the research efforts of Dr. Joshua Schiffman and Dr. Avi Schroeder, PEEL Therapeutics (PEEL) has created liposomal nanoparticles that have been loaded with elephant p53 (EP53) proteins as a new class of anti-cancer protein therapeutics. Elephants have an unexpectedly low rate of cancer given their large size (100 times that of humans) and longevity (lifespans of 50 to 70 years). When exposed to DNA damage, elephant cells undergo much more robust p53-triggered apoptosis (cell death) compared to human cells, effectively eliminating pre- cancerous cells with DNA mutations. Recent work has shown that human cancer cells undergo rapid and robust cell death when the EP53 protein is transduced and expressed. This EP53-induced apoptosis is especially pronounced in human osteosarcoma cells, one of the most common and deadly pediatric bone tumors. EP53 protein delivered by PEEL's nanoparticles (NPs) induces apoptosis in osteosarcoma cells in vitro. Osteosarcoma has not had a successful new therapeutic drug in over 40 years and represents a very large and unmet clinical need. For this Phase I STTR program, PEEL Therapeutics will move forward with testing of its EP53 protein NPs, and also will determine if adjuvant chemotherapy delivered prior to EP53 NP treatment increases the ability to kill cancer cells. For AIM 1, PEEL will select the most effective dose EP53 protein-loaded nanoparticles to cause apoptosis in different types of osteosarcoma cells, with and without adjuvant chemotherapy (in vitro). For AIM 2, PEEL Therapeutics will identify the maximum tolerated dose (MTD) for EP53 protein-loaded nanoparticles and demonstrate their efficacy in osteosarcoma patient derived xenograft (PDX) models (in vivo). After completing these Phase I STTR tasks, PEEL Therapeutics will be in an excellent position to advance its new and patented nanoparticle protein drug on the pathway to further preclinical studies, eventually culminating in first-in-human trials. These efforts by PEEL Therapeutics will lead to clinical improvements for the outcome of children and adolescents being treated for osteosarcoma ? a deadly bone tumor currently lacking new therapeutic options.